Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder characterized by extracellular deposits of A peptide in senile plaques, intraneuronal neurofibrillary tangles, synapse loss, and cognitive decline. It is widely believed that the accumulation of Aβ, a small peptide with a high propensity to form oligomers and aggregates, is central to the pathogenesis of AD. APP is cleaved by proteases including α,β, and γ-secretases, generating amyloid-β (Aβ) peptide, the main component of the amyloid plaques that are associated with Alzheimer's disease.
Aβ derives from the proteolytic cleavage of the transmembrane protein, APP. Although a considerable amount is known about interacting proteins and processing events for APP, the physiological role(s) of APP and its related family members, APLP1 and APLP2 (amyloid precursor-like proteins 1 and 2), is still poorly understood. APP has been proposed to function in cell adhesion and motility, as well as synaptic transmission and plasticity. The cloning and characterization of APP revealed that it possesses many features reminiscent of a membrane-anchored receptor. Compatible with this notion, APP was suggested to function as a single transmembrane G-protein coupled receptor. However, to date, no clear candidate has emerged as the major ligand triggering APP mediated signal transduction (although several molecules have been shown to bind APP, such as collagen (types I and IV), heparan sulfate proteoglycan, laminin, and glypican)—at least in part because the signal transduction mediated by APP remains incompletely understood.
Thus, there is a need for identification of molecules that bind APP and modulate APP signaling and AB peptide production. The present invention meets this need and provides related advantages.